The project proposes continuation of a comprehensive pediatric oncology program at Childrens Hospital of Los Angeles (CHLA). This program is designed to improve the treatment of children with cancer by conducting clinical investigations as a member of the Childrens Cancer Study Group (CCSG) and by independently conducting other research which is directly related to the mission of CCSG. CHLA is a major pediatric referral center for the Pacific Southwest and has one of the largest pediatric oncology services in the nation. An interdepartmental program has developed which involves basic and clinical scientists and has evolved into a multidisciplinary model for the management of pediatric cancers. participation of CHLA investigators in CCSG enables quantitative comparative clinical investigations aimed at establishing the best mode of any cancer therapy. The unique resources of CHLA permit development of new therapeutic approaches for Group-wide application. These include participation in the NCI Phase I Working Group and the Late Effects Study Group, Brain Tumor Program, Bone and Extremity Tumor Program, the evaluation of new dose schedules and combinations of established agents predicted by in vitro and in vivo pharmacological studies, investigation of mechanisms of drug resistance, bone marrow transplantation, immunological characterization of selected neoplasms, effects of cancer and its treatment on hematopoiesis, intensive chemotherapy in the protected environment, optimum nutritional support in childhood malignancies, approaches to psychosocial rehabilitation of the pediatric cancer patient and family, education of caregivers and patients/families, epidemiology of childhood malignancies, late effects of cancer and its treatment, preclinical studies in molecular and cellular pharmacology, tumor cell biology, carcinogenesis and chemoprevention, cytogenetics, and in vitro and in vivo tumor model system. A network of community physicians participates in the CCSG Cooperative Group Outreach Program under the sponsorship of CHLA which enables the use of optimal therapy in children who are not referred for initial cancer care. Through the proposed renewal, the comprehensive program at CHLA will seek as its ultimate goal an integrated and investigative approach to childhood cancer.